Cano tested positive for the diuretic furosemide, which violates MLB's drug prevention and treatment program. He said he would accept the suspension, which begins immediately.
"Recently I learned that I tested positive for a substance called Furosemide, which is not a performance enhancing substance," Cano said in a statement released by the MLB Players Association. "... For more than 15 years, playing professional baseball has been the greatest honor and privilege of my life. I would never do anything to cheat the rules of the game that I love, and after undergoing dozens of drug tests over more than a decade, I have never tested positive for a performance enhancing substance for the simple reason that I have never taken one."
Under MLB's drug policy, a player is not automatically suspended for use of a diuretic unless MLB can prove he intended to use it as a masking agent.
A source familiar with the case told ESPN's T.J. Quinn that Cano tested positive before the season and appealed. During the appeal, MLB apparently was able to determine his intent, which resulted in Cano dropping his appeal, the source said.
Cano said he was given furosemide by a licensed doctor in his native Dominican Republic and the substance is used to treat "various medical conditions" there and in the United States.
"While I did not realize at the time that I was given a medication that was banned, I obviously now wish that I had been more careful," Cano said.
Cano suffered a fractured fifth metacarpal in his right hand when he was struck by a pitch from Detroit's Blaine Hardy on Sunday. He was placed on the disabled list Monday and, according to multiple reports, had surgery Tuesday.
MLB said Cano's time on the disabled list will count toward his 80-game suspension. Baseball's drug program doesn't distinguish between a healthy and unhealthy player. However, he will lose salary -- $11.85 million of his $24 million deal for 2018, according to ESPN's Darren Rovell -- and is ineligible for the postseason and the All-Star Game.
"This was the most difficult decision I have ever made in my life, but ultimately the right decision given that I do not dispute that I was given this substance," Cano said in his statement, in reference to accepting the suspension. "I apologize to my family, friends, fans, teammates and the Mariners organization. I am extremely grateful for the support I have received during this process, and I look forward to rejoining my teammates later this season."
The Mariners issued a statement saying they were disappointed.
"Robinson made a mistake," the team's statement said. "He has explained to us what happened, accepted the punishment and has apologized to the fans, the organization and his teammates. We will support Robinson as he works through this challenge."
The 35-year-old second baseman spent the first nine years of his career with the New York Yankees, and news of his suspension shocked his former teammates.
"It's surprising because I know Robbie. But after the Ryan Braun thing, nothing surprises me," said Yankees left-hander CC Sabathia, who was teammates with Braun in Milwaukee before the Brewers slugger tested positive for PEDs.
Yankees outfielder Brett Gardner called Cano one of his favorite teammates.
"[The positive test] doesn't change how I felt about him as a teammate and the way that he was to me as a young player," Gardner said. "So unfortunate to hear that kind of news, especially somebody that you played with."
Cano is one of the Mariners' biggest stars. He hit 23 home runs last season and 39 in 2016.
The eight-time All-Star selection was batting .287 with four home runs and 23 RBIs this season, his fifth with Seattle. Before breaking his hand, Cano hadn't missed a game this season, and he hasn't played in fewer than 150 games in any of the past 11 seasons.
According to ESPN Stats & Information, Cano's 1,783 games played since the start of the 2007 season are the most in MLB in that span.
Current Mariners outfielder Dee Gordon was suspended 80 games for violating MLB's performance-enhancing drug policy while he was with the Marlins in 2016. Mariners general manager Jerry Dipoto said Gordon, a former second baseman, will likely see some time at that position to fill in for the suspended Cano.
Current designated hitter Nelson Cruz served a 50-game suspension while with the Rangers in 2013 for violations of the drug agreement, in relation to the sport's investigation of the Biogenesis of America clinic.
ESPN's Jerry Crasnick and Coley Harvey contributed to this report.